The UK’s most senior diplomat in Brussels, Jonathan Hill, is resigning following Britain’s vote to leave the European Union, as “what is done cannot be undone”.

Lord Hill, the UK’s European commissioner, was sent to Brussels by David Cameron and took the highly prized portfolio of financial services. But his departure from a big EU finance job became a foregone conclusion after the vote for Brexit, because many European politicians oppose having a Briton in charge of financial services when the UK is on its way out.

Several MEPs had already called on Hill to be stripped of his crucial economic portfolio.

Hill said he did not think it was right he carried on as British commissioner as if nothing had happened.

The Conservative peer, who once campaigned to keep Britain from joining the euro, said he had arrived in Brussels as someone who was sceptical about Europe, but would leave “certain that, despite its frustrations, our membership was good for our place in the world and good for our economy. But what is done cannot be undone and now we have to get on with making our new relationship with Europe work as well as possible.”

A former adviser to John Major and Ken Clarke, Hill joined the commission in 2014. He was given the portfolio of financial markets in a peace-making gesture from the European commission president, Jean-Claude Juncker, towards the British government.

Juncker’s decision to award the crucial finance portfolio to a Briton was intended to pour oil on troubled waters, after David Cameron tried to block Juncker’s appointment.

In a respectful statement of thanks, Juncker said he had tried to persuade Hill to stay on as a commissioner, describing the Conservative peer as “a true European and not just the British commissioner”.

The commission president had wanted a Briton in charge of financial services “as a sign of my confidence in the United Kingdom’s membership of the European Union. To my great regret, this situation is now changing.”

Hill’s last day will be on 15 July. In a move heavy with symbolism, he will pass over the financial services portfolio to Valdis Dombrovskis, the commission vice-president in charge of the euro.

Each EU member state has a commissioner in Brussels, although their job is to represent common European interests, not national ones. Despite that mission, successive British governments have lobbied to get a big financial dossier for the British commissioner, in a bid to safeguard the interests of the City of London.

The European commission is the EU civil service but is led by political appointees such as Hill, who are responsible for initiating and enforcing EU laws. Contrary to popular myth, European commissioners do not make EU laws. National governments and elected MEPs agree EU laws that have been drafted by the commission.

Hill’s sudden departure leaves the UK’s position in the commission hierarchy unclear, adding to the many unanswered questions about Brexit.

The UK retains the rights and duties of membership until it formally leaves the union and is obliged to send a new commissioner to Brussels. The commission said it was ready “to discuss swiftly” with Cameron a replacement for Hill, as well as a potential portfolio.

Sources said the new British commissioner could expect a much less important job. Prior to going to Brussels, Hill served from the House of Lords as an education minister in the Conservative-Liberal Democrat coalition.

In the weeks leading up to the referendum, Hill told the Guardian that a vote to remain could be an opportunity to reset Britain’s relationship with the rest of Europe, adding that he saw “a lot of opportunity for the UK to help shape the future direction that Europe takes”.

His departure underscores how the British relationship with the EU will now be reset in a radically different way than that he had hoped for.

A Downing Street spokesman said: “The prime minister is sorry that Lord Hill has decided to step down. He is extremely grateful to Lord Hill for his service at the European commission in the crucial portfolio of financial stability, financial services and capital markets union.

“He has done an excellent job as a commissioner, helping to focus the European commission on measures to promote growth and jobs, in particular his proposals to increase the flow of affordable investment capital across the EU and for giving the UK a strong voice in the European commission. The prime minister wishes Lord Hill well for the future.”

The spokesman said a decision on a future British commissioner would fall to Cameron’s successor: “It will be for the next prime minister to decide, following discussions with European partners, what role the UK plays in the European commission, given we remain a full member of the EU until we have left.”